Responses of human T cells against mycobacteria and mycobacterial components were analysed. T cells expressing either the alpha/beta or the gamma/delta T cell receptor were selected from human peripheral blood lymphocytes and proliferative responses to intact mycobacteria and to molecular mass-fractionated mycobacterial lysates were determined. alpha/beta T cells responded primarily to fractions greater than 30 kDa. Protease digestion abolished the stimulating activities for alpha/beta T cells, confirming that alpha/beta T cells respond to protein components. In contrast components recognized by gamma/delta T cells proved resistant to protease digestion. In limiting dilution studies, frequencies of proliferating gamma/delta T cells remained virtually unaltered by protease treatment of stimulating lysates, while those of alpha/beta T cells became almost undetectable. Furthermore, only few gamma/delta T cells responded to the 65 kDa heat shock protein. Our data indicate that, unlike alpha/beta T cells, gamma/delta T cells respond to mycobacterial components which are resistant to vigorous protease digestion.